Abstract 3342: The dark age of single organ screening is over: CD24 is a novel universal pan-cancer blood test for early detection of cancer
Authors: Fatin Madah, Dina Kazanov, Mays Motlaq, Lihi Argaman, Meital Shaked, Gil Shenberg, Yael Hofman, Miri Sror, Michael Peer, Dan Greissaro, Michael Tepper, Marina Ben-Shimon, Lior Galazan, Ido Wolf, Shiran Shapira, Nadir Arber
Journal: Cancer Research (2023)

Abstract Background: Early detection offers the best chance of cure. Screening separately for different cancer types is time-consuming, less economically efficient and has poor compliance rates. Pan-cancer screening liquid biopsy that can detect most common cancer types may shift the paradigm in the treatment of cancer through early detection and prevention. CD24, a cell surface, heavily glycosylated GPI-anchored mucin-like protein is express in all/most cancers but very rarely on normal cells. Aim: To evaluate the feasibility of a universal pan-cancer screening blood test (cancerD24), and to design a model (PANDEX) that discriminate between healthy and cancer subjects with a high level of accuracy. Methods: Blood samples and informed consent were obtained from 464 consecutive cancer patients and 1,138 matched (gender, age, medical history) healthy volunteers attending the Tel Aviv Medical Center. 1x106 leukocytes were stained using anti-CD11b-PerCp-Cy5 and anti-CD24-FITC and analyzed by flow cytometry. Percentage of positive cells was determined by subtracting the percentage of CD24 and CD11b-positive cells (dual stain) from CD24-positive cells (single stain). The healthy subjects underwent a thorough evaluation including examination, imaging and blood tests by specialists in internal medicine, surgery, plastic surgery, oncology, oral surgery, gastroenterology and other specialties. Women underwent a vaginal ultrasound and HPV, mammography and US/MRI when indicated. Men underwent PSA and free PSA testing and testicular and rectal examination by urologist. Moderate and heavy smokers were screened with low-dose CT. All cancers were verified histologically. A logistic regression was fitted univariately on CD24, both as continuous and categorical variables. A sensitivity analysis of model discrimination ability was performed using a bootstrap cross-validation method. Results: Cancer types were categorized into 21 major groups. 52% and 50% were healthy/cancer females. CD24/CD11b expression in peripheral blood leukocytes (PBLs) of healthy participants (21±1) was found to be statistically significantly lower than of cancer patients (33±2) and polyps (32±2) with high sensitivity (87%) and specificity (87%) (P&amp;lt;0.01). An AUC metric for generalized linear models was developed using gender, age and with an predictive ability of 0.95. In several types of cancer (CRC, LY, oral cancer), the level dropped back to near normal level following surgery/chemotherapy. Increase in CD24/CD11b expression is an early event in the multi-step process of carcinogenesis as there was no difference in the expression levels regardless cancer stage (TNM 0-4). Conclusions: CancerenD24 may serves as a universal blood test as an aid to clinicians in the early detection of many cancers. The first ever blood test to detect pre-malignant lesions. The test is GLP-compliant, reliable and relatively simple. Citation Format: Fatin Madah, Dina Kazanov, Mays Motlaq, Lihi Argaman, Meital Shaked, Gil Shenberg, Yael Hofman, Miri Sror, Michael Peer, Dan Greissaro, Michael Tepper, Marina Ben-Shimon, Lior Galazan, Ido Wolf, Shiran Shapira, Nadir Arber. The dark age of single organ screening is over: CD24 is a novel universal pan-cancer blood test for early detection of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3342.